A5067636527- Alzheimer's disease research and treatments
- Parkinson's Disease Mechanisms and Treatments
- Neurological disorders and treatments
- Neuroscience and Neuropharmacology Research
- Cholinesterase and Neurodegenerative Diseases
- Computational Drug Discovery Methods
- Botulinum Toxin and Related Neurological Disorders
- T-cell and B-cell Immunology
- Mitochondrial Function and Pathology
- Immunotherapy and Immune Responses
- Synthesis and pharmacology of benzodiazepine derivatives
- Machine Learning in Bioinformatics
- RNA and protein synthesis mechanisms
- Biotin and Related Studies
- Glycosylation and Glycoproteins Research
- Cancer Treatment and Pharmacology
- Carbohydrate Chemistry and Synthesis
- Photochromic and Fluorescence Chemistry
- Immune Cell Function and Interaction
- S100 Proteins and Annexins
- Lymphatic System and Diseases
- Genomics and Chromatin Dynamics
- Dementia and Cognitive Impairment Research
- Nicotinic Acetylcholine Receptors Study
- Advanced MRI Techniques and Applications
AC Immune (Switzerland)
2013-2025
University Hospital of Lausanne
2024
Weatherford College
2024
École Polytechnique Fédérale de Lausanne
2014-2023
University of Lausanne
2007-2011
Dendritic cells (DCs), and more recently lymph node stromal (LNSCs), have been described to tolerize self-reactive CD8+ T in LNs. Although LNSCs express MHCII, it is unknown whether they can also impact CD4+ cell functions. We show that the promoter IV (pIV) of class II transactivator (CIITA), master regulator MHCII expression, controls endogenous expression by LNSCs. Unexpectedly, acquire peptide–MHCII complexes from DCs induce dysfunction presenting transferred naive preventing their...
Abstract Until recently, the known roles of lymphatic endothelial cells (LECs) in immune modulation were limited to directing cell trafficking and passively transporting peripheral Ags lymph nodes. Recent studies demonstrated that LECs can directly suppress dendritic maturation present tissue tumor for autoreactive T deletion. We asked whether play a constitutive role deletion under homeostatic conditions. In this study, we demonstrate murine noninflamed conditions actively scavenge...
Tau deposition is a key pathological feature of Alzheimer's disease (AD) and other neurodegenerative disorders. The spreading tau neurofibrillary tangles across defined brain regions corresponds to the observed level cognitive decline in AD. Positron-emission tomography (PET) has proved be an important tool for detection amyloid-beta (Aβ) aggregates brain, currently being explored misfolded AD non-AD tauopathies. Several PET tracers targeting deposits have been discovered tested humans....
A positron emission tomography (PET) tracer detecting α-synuclein pathology will improve the diagnosis, and ultimately treatment of α-synuclein-related diseases. Here we show that PET ligand, [
Abstract Background Tau is an intracellular protein that plays a crucial role in stabilizing microtubules. However, it can aggregate into various forms under pathological conditions and be secreted the brain parenchyma. While consequences of tau aggregation within neurons have been extensively studied, effects extracellular paired helical filaments (ePHF-tau) on astrocytes are still poorly understood. Methods This study examined effect human ePHF-tau (2N4R) primary cultures rat neuroglia,...
Site-specific proteolytic processing plays important roles in the regulation of cellular activities. The histone modification activity human trithorax group mixed-lineage leukemia (MLL) protein and cell cycle regulatory proliferation factor herpes simplex virus host 1 (HCF-1) are stimulated by cleavage precursors that generates stable heterodimeric complexes. MLL is processed a protease called taspase 1, whereas precise mechanisms HCF-1 maturation unclear, although they known to depend on...
The first candidate PI-2014 was tested in healthy controls and subjects with Alzheimer's disease (AD). As displayed off-target binding to monoamine oxidase A (MAO-A), a new lead improved Tau decreased MAO-A required. For compound optimization, assays based on both human AD brain homogenate Tau-paired helical filaments were employed. Furthermore, two screening (1) human-recombinant (2) displacement of 2-fluoro-ethyl-harmine from mouse Removing the N-methyl group tricyclic core resulted...
Abstract Background To study the ability of newly developed α‐synuclein Positron Emission Tomography (PET) tracer, [ 18 F]ACI‐12589, created and by AC Immune SA, to detect neuropathology in vivo , clinically diagnosed patients with α‐synucleinopathies. Method We intend scan a total up 50 participants different diseases associated age‐ gender‐matched controls. These will include Parkinson’s disease (PD), Multiple System Atrophy (MSA), Dementia Lewy bodies (DLB), or caused duplication gene,...
Intracellular tau deposition is a key pathologic feature of Alzheimer's disease (AD) and other neurodegenerative disorders. Recently, positron emission tomography probes have been developed for in vivo detection brain load, although quantification challenging due to high off-target binding slow kinetics. Further, different radiotracers affinities species. PI-2620 novel tracer with an IC50 1.8 nM AD homogenate competition-assays binds specifically deposits sections (Braak I-VI), Pick's,...
Abstract Background The progressive accumulation of aggregated alpha‐synuclein (a‐syn) in the form Lewy bodies and neurites is hallmark e.g. Parkinson’s disease (PD). Due to low density a‐syn pathology frequency co‐existing proteinopathies PD (e.g., beta‐amyloid, tau), an PET tracer must display high binding affinity selectivity target, as well minimal background. Method [ 18 F]‐ACI‐Cpd‐AE was evaluated a first‐in‐human (FiH) study. dynamic imaging conducted over 90 min five subjects (four...
Tau aggregates represent a critical pathology in Alzheimer's disease (AD) and other forms of dementia. The spreading neurofibrillary tangles across defined brain regions corresponds to the observed level cognitive decline AD. Positron emission tomography has proved be an important tool for detection amyloid-beta is currently explored AD tauopathies. Several tracers targeting have been discovered tested humans so far. However, limitations reported especially regarding their selectivity...
Abstract Background Parkinson’s disease (PD) and other alpha‐synucleinopathies are characterized by the progressive accumulation of alpha‐synuclein (a‐syn) inclusions in brain, which start pre‐motor stage correlates with its severity. An imaging agent for a‐syn could allow differential diagnosis support interventional trails. AC Immune has developed is currently testing a first human (FiH) clinical trial recently discovered compound, ACI‐12589, as PET tracer high affinity selectivity a‐syn....
Abstract Background Parkinson’s disease (PD) and other synucleinopathies such as Multiple System Atrophy (MSA) involve a progressive accumulation of a‐synuclein (a‐syn) inclusions that correlates with stage clinical manifestations. The development PET agent capable imaging a‐syn would significantly aid in differential diagnosis, staging, monitoring possible benefits candidate therapeutic agents targeting a‐syn. Due to the generally lower pathologic burden relative brain proteinopathies,...
Abstract Background Tauopathies encompass a spectrum of neurodegenerative disorders which are marked by the pathological aggregation tau protein into paired helical filaments (PHF-tau), neurofibrillary tangles (NFTs) and Glial-fibrillary (GFTs). These aggregates impair cellular, mitochondrial, synaptic functions. The emergence extracellular (ePHF-tau), featuring myriad isoforms phosphorylation states, presents challenge in comprehending its nuanced effects on neural cells, particularly...
<title>Abstract</title> <bold>Background</bold> Tauopathies encompass a spectrum of neurodegenerative disorders which are marked by the pathological aggregation tau protein into paired helical filaments (PHF-tau), neurofibrillary tangles (NFTs) and Glial-fibrillary (GFTs). These aggregates impair cellular, mitochondrial, synaptic functions. The emergence extracellular (ePHF-tau), featuring myriad isoforms phosphorylation states, presents challenge in comprehending its nuanced effects on...
<title>Abstract</title> Biomarkers that facilitate early detection and track disease progression are an enormous unmet need in neurodegenerative diseases their clinical trials. Accurate diagnosis the stage of Parkinsonian disorders is particularly challenging. Multiple system atrophy (MSA) Parkinson’s (PD) share many features associated with alpha-synuclein (αSyn) aggregation. However, these have distinct biology trajectories likely to respond differently experimental therapies....
Tau aggregates represent a critical pathology in Alzheimer's disease (AD) and other forms of dementia. The spreading neurofibrillary tangles across defined brain regions corresponds to the observed level cognitive decline AD. Positron emission tomography has proved be an important tool for detection amyloid-beta is currently explored AD tauopathies. Several tracers targeting have been discovered tested humans so far. However, limitations reported especially regarding their selectivity...
The brain of patients with Alzheimer's disease (AD) is characterized by plaques and neurofibrillary tangles (NFT) composed misfolded protein aggregates beta-amyloid hyper-phosphorylated tau, respectively. Immunotherapy can alleviate the pathological impact protein-aggregates as demonstrated in several animal models. correlation between cognitive decline number NFT AD suggests phosphorylated tau (pTau) a promising target for immunotherapy. Tau transgenic mice were immunized over 6-month...
Abstract Background Parkinson’s disease (PD) and other synucleinopathies, such as Multiple System Atrophy (MSA), involve a progressive accumulation of a‐synuclein (a‐syn) inclusions which correlate well with clinical manifestations. A PET agent capable imaging specifically selectively a‐syn could significantly improve differential diagnosis trials for drug candidates targeting a‐syn. Here, we report the preclinical initial characterization [ 18 F]ACI‐12589 in patients different...
The accumulation of aggregated alpha-synuclein (aSyn) in form Lewy bodies and neurites is the pathognomonic signature patients with Parkinson's disease (PD) other synucleinopathies. Currently, diagnosis PD synucleinopathies largely based on symptomatic evaluation patients. direct association between progressive formation aSyn inclusions severity clinical symptoms supports development PET tracers for non-invasive examination aggregates human brain as an objective diagnostic tool applications....